SIGNIFICANT LOSS OF PYRAMIDAL NEURONS IN THE ANGULAR GYRUS OF PATIENTS WITH HUNTINGTONS-DISEASE

The primary site of pathology in Huntington's disease (HD) is the caud ate nucleus. However, cortical changes are also commonly reported. Whi le many researchers have studied pathology in the frontal lobe, little attention has been paid to posterior cortical regions. The aim of thi s study is to examine pathology in the parietal lobe in patients with HD as it has specific projections to the caudate nucleus. Post-mortem brain tissue was obtained from HD patients with both a positive family history and clinicopathological diagnosis (n = 6; Vonsattel grades 2- 4) as well as from neurologically normal controls (n = 6). The angular gyrus of the parietal lobe was sampled and cellular quantification of SMI-32 immunohistochemically detected pyramidal neurons performed. Co rtical blocks were sectioned at 50 mu m on a cryostat and stained immu nohistochemically using antigen retrieval methods and peroxidase visua lization. HD subjects had noticeable histological changes including sm aller neurons and a disruption of cortical laminar pattern. Quantifica tion using a point counting method to find the areal fraction of immun oreactive neurons revealed a severe loss of pyramidal neurons in the a ngular gyrus of HD subjects compared with controls (reduced on average to 55% of mean control values, P = 0.038 using the Mann-Whitney U-tes t), This striking cortical pathology suggests that HD may preferential ly target posterior cortical regions, particularly the angular gyrus w hich has a significant projection to the caudate nucleus in primates.